Drug interactions
Amitriptyline + Donepezil
Severity: Moderate
Amitriptyline and Donepezil: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Donepezil enhances cholinergic transmission while amitriptyline blocks muscarinic receptors, so the two have opposing actions and may reduce the cognitive benefit of donepezil. Both agents can also prolong the QT interval, and donepezil may cause bradycardia, raising arrhythmia risk.
What this interaction means in plain words
Amitriptyline and Donepezil can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Amitriptyline belongs to Central Nervous System; Donepezil belongs to Central Nervous System.
Why it happens
Pharmacodynamic antagonism between a cholinesterase inhibitor and an anticholinergic tricyclic, plus additive QT prolongation.
What to do
Avoid amitriptyline in dementia patients when possible and consider a less anticholinergic antidepressant. If combined, monitor cognition, heart rate and ECG, and correct potassium and magnesium.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Donepezil
- Donepezil + Dronedarone Contraindicated
- Donepezil + Pimozide Contraindicated
- Donepezil + Thioridazine Contraindicated
- Donepezil + Vandetanib Contraindicated
- Amiodarone + Donepezil Major
- Amisulpride + Donepezil Major
Frequently asked questions
Can I take Amitriptyline with Donepezil?
MediHelp rates the interaction as moderate. Amitriptyline and Donepezil can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Donepezil enhances cholinergic transmission while amitriptyline blocks muscarinic receptors, so the two have opposing actions and may reduce the cognitive benefit of donepezil. Both agents can also prolong the QT interval, and donepezil may cause bradycardia, raising arrhythmia risk.
How serious is the interaction between Amitriptyline and Donepezil?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid amitriptyline in dementia patients when possible and consider a less anticholinergic antidepressant. If combined, monitor cognition, heart rate and ECG, and correct potassium and magnesium.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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